Target Validation Information
TTD ID	TTDC00292
Target Name	Alpha-1A adrenergic receptor
Type of Target	Clinical trial target
Drug Potency against Target	Dutasteride & tamsulosin		IC50 = 6 nM	[1]
	WAY-100135		IC50 = 1490 nM	[2]
	ATC-0175		IC50 = 300 nM	[3]
	Siramesine		IC50 = 330 nM	[4]
	ISOCLOZAPINE		IC50 = 64 nM	[5]
	ABANOQUIL		Ki = 0.03 nM	[6]
	SILODOSIN		Ki = 0.036 nM	[7]
	(+)-NIGULDIPINE		Ki = 0.16 nM	[7]
	SNAP-7915		Ki = 0.17 nM	[7]
	(-)-SNAP-5089		Ki = 0.18 nM	[7]
	MAZAPERTINE		Ki = 0.2 nM	[8]
	SNAP-6201		Ki = 0.2 nM	[7]
	A-131701		Ki = 0.22 nM	[7]
	RS-100329		Ki = 0.25 nM	[7]
	WB-4101		Ki = 0.35 nM	[6]
	L-771688		Ki = 0.36 nM	[7]
	(-)-SNAP-5399;SNAP-5399		Ki = 0.4 nM	[7]
	RS-17053		Ki = 0.6 nM	[7]
	RWJ-69736		Ki = 0.65 nM	[7]
	OCTOCLOTHEPIN		Ki = 0.66 nM	[9]
	FLUANISONE		Ki = 0.87 nM	[10]
	UPIDOSIN		Ki = 1 nM	[7]
	Ro-700004;RS-100975		Ki = 1.3 nM	[7]
	SNAP-5089		Ki = 1.3 nM	[11]
	TIOSPIRONE		Ki = 1.5 nM	[12]
	NIGULDIPINE		Ki = 1.8 nM	[11]
	SNAP-5150		Ki = 1.9 nM	[7]
	(2-Bromo-phenyl)-(1H-imidazol-2-yl)-amine		Ki = 11000 nM	[13]
	Imidazolidin-2-ylidene-quinoxalin-6-yl-amine		Ki = 11000 nM	[14]
	MEDETOMIDINE		Ki = 1102 nM	[15]
	R-226161		Ki = 125 nM	[16]
	SNAP-8719		Ki = 1400 nM	[17]
	5-Bromo-8-piperazin-1-yl-imidazo[1,2-a]pyrazine		Ki = 1490 nM	[18]
	4-(3-Hydroxy-piperidin-3-yl)-benzene-1,2-diol		Ki = 15000 nM	[19]
	N-(5-Bromo-quinoxalin-6-yl)-guanidine		Ki = 17000 nM	[14]
	4-(1-Naphthalen-1-yl-vinyl)-1H-imidazole		Ki = 1734 nM	[20]
	4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one		Ki = 18 nM	[21]
	SNAP-94847		Ki = 180 nM	[22]
	(+/-)-nantenine		Ki = 2 nM	[23]
	A-119637		Ki = 2.6 nM	[7]
	RWJ-68157		Ki = 22 nM	[7]
	1-Pyridin-2-yl-piperazine		Ki = 2400 nM	[24]
	Imidazolidin-2-ylidene-o-tolyl-amine		Ki = 2500 nM	[14]
	RX-821002		Ki = 27 nM	[25]
	CORYNANTHEINE		Ki = 29 nM	[7]
	BMY-7378		Ki = 290 nM	[17]
	NAFTOPIDIL		Ki = 3.7 nM	[7]
	8-Piperazin-1-yl-imidazo[1,2-a]pyrazine		Ki = 3100 nM	[18]
	4-(3,4-Dihydro-1H-isoquinolin-2-yl)-quinoline		Ki = 3200 nM	[26]
	BP-897		Ki = 33 nM	[27]
	SK&F-104078;SK-104078		Ki = 33 nM	[11]
	SK&F-105854;SK-105854		Ki = 3300 nM	[7]
	4-Benzo[b]thiophen-4-yl-1H-imidazole		Ki = 343 nM	[28]
	sunepitron		Ki = 35 nM	[29]
	1-(2-Methoxy-phenyl)-piperazine		Ki = 3508 nM	[30]
	SK&F-104856;SK-104856		Ki = 36 nM	[11]
	4-((E)-1-Naphthalen-1-yl-propenyl)-1H-imidazole		Ki = 387 nM	[20]
	A-123189		Ki = 4.2 nM	[7]
	SNAP-5036		Ki = 4.4 nM	[7]
	1',2',3',6'-Tetrahydro-[2,4']bipyridinyl		Ki = 4000 nM	[24]
	RS-513815		Ki = 41 nM	[7]
	L-765314		Ki = 420 nM	[7]
	SK&F-86466;SK-86466		Ki = 449 nM	[11]
	AGN-193080		Ki = 470 nM	[14]
1-(3-Fluoro-pyridin-2-yl)-4-methyl-piperazine		Ki = 490 nM	[24]
A-315456		Ki = 490 nM	[7]
Ro-11-04253		Ki = 5 nM	[7]
4-(1-Naphthalen-1-yl-ethyl)-1H-imidazole		Ki = 536 nM	[15]
4-(2,3-Dihydro-1H-phenalen-1-yl)-1H-imidazole		Ki = 55 nM	[20]
4-((Z)-1-Naphthalen-1-yl-propenyl)-1H-imidazole		Ki = 57 nM	[20]
4-(1-Naphthalen-1-yl-propyl)-1H-imidazole		Ki = 574 nM	[20]
SK&F-106686;SK-106686		Ki = 58 nM	[11]
2-Pyridin-4-yl-1,2,3,4-tetrahydro-isoquinoline		Ki = 5800 nM	[26]
RWJ-68141		Ki = 59 nM	[7]
(2,6-Dichloro-phenyl)-(1H-imidazol-2-yl)-amine		Ki = 6000 nM	[13]
UH-301		Ki = 6080 nM	[2]
4-(4-Isopropyl-morpholin-2-yl)-benzene-1,2-diol		Ki = 6700 nM	[19]
SPIPERONE		Ki = 7.9 nM	[7]
1-(2-Chloro-phenyl)-piperazine		Ki = 710 nM	[30]
4-(4-Methyl-indan-1-yl)-1H-imidazole		Ki = 73 nM	[31]
4-Morpholin-2-yl-benzene-1,2-diol		Ki = 7400 nM	[19]
RWJ-25730		Ki = 8.2 nM	[8]
AGN-192172		Ki = 8900 nM	[14]
RWJ-38063		Ki = 9.3 nM	[7]
2-(4-tert-Butyl-phenyl)-4,5-dihydro-1H-imidazole		Ki = 91 nM	[32]
LEVONORDEFRIN		Ki = 9221 nM	[20]
Action against Disease Model	Alfuzosin		Alfuzosin significantly prolonged action potential duration (APD)(60) in rabbit Purkinje fibers (p < 0.05) and QT in isolated rabbit hearts (p < 0.05) at the clinically relevant concentration of 300 nM. In man, the QT interval corrected with Fridericia's formula increased 7.7 ms, which exceeds the 5.0-ms threshold for a positive TCQS. Effects on hK(v)11.1, hK(v)4.3, and hK(v)7.1/hKCNE1 potassi uM currents and calci uM current were not involved. At 300 nM, approximately 30x C(max), alfuzosin significantly increased whole-cell peak sodi uM (hNa(v)1.5) current (p < 0.05), increased the probability of late hNa(v)1.5 single-channel openings, and significantly shortened the slow time constant for recovery from inactivation.	[33]
The Effect of Target Knockout, Knockdown or Genetic Variations	Alpha 1A-AR knockout mice: cardiac development is normal,cardiac function has decreased contraction and pressor response is decreased to PE			[34]
Ref 1	Prostate. 2004 Feb 1;58(2):130-44.Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. To Reference
Ref 2	J Med Chem. 1997 Apr 11;40(8):1252-7.N-[2-[(substituted chroman-8-yl)oxy]ethyl]-4-(4-methoxyphenyl)butylamines: synthesis and wide range of antagonism at the human 5-HT1A receptor. To Reference
Ref 3	Bioorg Med Chem Lett. 2009 Nov 1;19(21):6166-71. Epub 2009 Sep 6.Pyrimidine-based antagonists of h-MCH-R1 derived from ATC0175: in vitro profiling and in vivo evaluation. To Reference
Ref 4	J Med Chem. 1995 May 26;38(11):1998-2008.Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 1. 3-(omega-aminoalkyl)-1H-indoles. To Reference
Ref 5	J Med Chem. 1997 Dec 5;40(25):4146-53.Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine: identification of a novel atypical neuroleptic. To Reference
Ref 6	J Med Chem. 1995 Sep 1;38(18):3415-44.Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. To Reference
Ref 7	Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. To Reference
Ref 8	J Med Chem. 1994 Apr 15;37(8):1060-2.A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. To Reference
Ref 9	J Med Chem. 2010 Oct 14;53(19):7021-34.Exploring the neuroleptic substituent in octoclothepin: potential ligands for positron emission tomography with subnanomolar affinity for ¦Á(1)-adrenoceptors. To Reference
Ref 10	J Med Chem. 1987 Nov;30(11):2099-104.2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1. To Reference
Ref 11	J Med Chem. 1995 Sep 15;38(19):3681-716.Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. To Reference
Ref 12	J Med Chem. 1996 Jan 5;39(1):143-8.3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. To Reference
Ref 13	J Med Chem. 1997 Jan 3;40(1):18-23.Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists. To Reference
Ref 14	Bioorg. Med. Chem. Lett. 5(15):1745-1750 (1995) To Reference
Ref 15	J Med Chem. 1994 Jul 22;37(15):2328-33.A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic receptors. To Reference
Ref 16	Bioorg Med Chem. 2007 Jun 1;15(11):3649-60. Epub 2007 Mar 21.Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism. To Reference
Ref 17	J Med Chem. 2005 Apr 21;48(8):3076-9.Synthesis and structure-activity relationship of fluoro analogues of 8-{2-[4-(4-methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione as selective alpha(1d)-adrenergic receptor antagonists. To Reference
Ref 18	J Med Chem. 1992 Oct 16;35(21):3845-57.Synthesis and hypoglycemic activity of substituted 8-(1-piperazinyl)imidazo[1,2-a]pyrazines. To Reference
Ref 19	J Med Chem. 1992 Mar 20;35(6):1009-18.Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors. To Reference
Ref 20	J Med Chem. 1996 Jul 19;39(15):3001-13.Medetomidine analogs as alpha 2-adrenergic ligands. 2. Design, synthesis, and biological activity of conformationally restricted naphthalene derivatives of medetomidine. To Reference
Ref 21	J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 22	J Med Chem. 2007 Aug 9;50(16):3883-90.Synthesis and SAR investigations for novel melanin-concentrating hormone 1 receptor (MCH1) antagonists part 2: A hybrid strategy combining key fragments of HTS hits. To Reference
Ref 23	Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31. Epub 2009 Nov 20.Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. To Reference
Ref 24	J Med Chem. 1984 Sep;27(9):1182-5.Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines. To Reference
Ref 25	J Med Chem. 1986 Oct;29(10):2000-3.Alpha-adrenoreceptor reagents. 4. Resolution of some potent selective prejunctional alpha 2-adrenoreceptor antagonists. To Reference
Ref 26	Bioorg Med Chem Lett. 2003 May 19;13(10):1759-62.4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists. To Reference
Ref 27	J Med Chem. 2003 Aug 28;46(18):3822-39.Synthesis and pharmacological evaluation of potent and highly selective D3 receptor ligands: inhibition of cocaine-seeking behavior and the role of dopamine D3/D2 receptors. To Reference
Ref 28	J Med Chem. 2000 Mar 9;43(5):765-8.alpha(2) Adrenoceptor agonists as potential analgesic agents. 2. Discovery of 4-(4-Imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene [corrected] as a high-affinity ligand for the alpha(2D) adrenergic receptor. To Reference
Ref 29	J Med Chem. 2006 Jun 1;49(11):3116-35.An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. To Reference
Ref 30	J Med Chem. 1991 Jun;34(6):1850-4.Pyrimido[5,4-b]indole derivatives. 1. A new class of potent and selective alpha 1 adrenoceptor ligands. To Reference
Ref 31	J Med Chem. 1997 Sep 12;40(19):3014-24.Medetomidine analogs as alpha 2-adrenergic ligands. 3. Synthesis and biological evaluation of a new series of medetomidine analogs and their potential binding interactions with alpha 2-adrenoceptors involving a "methyl pocket". To Reference
Ref 32	Bioorg Med Chem Lett. 2004 Sep 20;14(18):4697-9.2-(Anilino)imidazolines and 2-(benzyl)imidazoline derivatives as h5-HT1D serotonin receptor ligands. To Reference
Ref 33	J Pharmacol Exp Ther. 2008 Feb;324(2):427-33. Epub 2007 Nov 6.Alfuzosin delays cardiac repolarization by a novel mechanism. To Reference
Ref 34	Life Sci. 2002 Sep 27;71(19):2207-15.Transgenic studies of alpha(1)-adrenergic receptor subtype function. To Reference

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.

Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore

All rights reserved.